Human herpesviruses all have considerable clinical importance and persist in most individuals as long-term latent infections associated with either neurones for lymphocytes. In this project we have been characterizing and comparing the detailed structural organization of the complex genomes of these viruses with special emphasis at present on cytomegaloviruses and varicella-zoster virus. Our research also concentrates on molecular aspects of vival gene regulation in cultured cells infected with either herpes simplex virus, human cytomegalovirus or simian cytomegalovirus. We have been particulary interested in the very earliest events occurring in both permissive and non-permissive infections and in isolating and characterizing the viral immediate-early genes and their promoter sequences. We are to attempting to reconstruct some of these regulatory processes in microinjected oocytes or mammalian cell culture systems. Projects in progress include: (1) Examination of homology and structural relationships amongst the genomes of several subgroups of primate and mammalian cytomegaloviruses, (2) Study of the extent of distribution of the alternating (CA)n regions in different CMV genomes, (3) A search for homology between varicella-zoster virus and other related herpesviruses, (4) Expression of the IE 175K and other IE genes of HSV-2 and IE94 from simian CMV in short-term transfections and permanent cell lines, (5) The mechanism of the regulatory "switch-on" of hybrid interferon genes under the control of herpesvirus immediate-early and delayed-early promoters, (6) Nature of the tight block to expression of simian CMV delayed-early genes in non-permissive rodent cells, (7) Structure and DNA sequence of the simian CMV IE94 gene and promoter region, and (8) Use of the simian CMV IE94 promoter for strong constitutive expression of foreign genes in transfected eukaryotic cells.